Oral bioavailability and pharmacokinetics of esculetin following intravenous and oral administration in rats

Abstract

1. Esculetin is the main active ingredient isolated from Artemisia montana (Nakai) Pamp. and Euphorbia lathyris L. The present study investigated the oral bioavailability and pharmacokinetics of esculetin in rats, following intravenous and oral administration.

2. Twenty Sprague-Dawley rats were randomly assigned to receive 10 mg/kg of esculetin either by the intravenous or oral route. Plasma concentrations of esculetin were measured using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated using non-compartmental analysis as well as a compartmental modelling approach using WinNonlin^TM and ADAPT 5 software, respectively.

3. According to non-compartmental analysis, the mean oral bioavailability of esculetin was 19%. Mean ± standard deviation values of esculetin half-life, steady-state volume of distribution and clearance, following intravenous dosing, were 2.08 ± 0.46 h, 1.81 ± 0.52 L/kg and 1.27 ± 0.26 L/h/kg, respectively. As indicated by compartmental modelling, a two-compartment pharmacokinetic model with first-order absorption and elimination rate constants of 0.98 ± 0.18 h⁻¹ and 2.47 ± 0.28 h⁻¹, respectively, sufficiently described the plasma concentration–time curve of esculetin.

4. Improving our understanding of the pharmacokinetic properties of esculetin could help with future development of herbal medicine products with appropriate bioactivity.

Keywords:

• Esculetin
• pharmacokinetics
• bioavailability
• modelling
• herbal medicine

Author contributions

Kwak, J.H., Kim, Y., and Baek, I.H. conceived and designed the experiments. Kwak, J.H. and Baek, I.H. performed the LC-MS/MS analysis. Kim, Y. and Baek, I.H. performed the animal experiments. Staatz, C.E. and Baek, I.H. analysed the pharmacokinetic data. Kwak, J.H., Staatz, C.E., and Baek, I.H. wrote the manuscript. All authors have read and approved the final version of the manuscript.

Disclosure statement

The authors declare that there are no conflicts of interest.

Additional information

Funding

The authors are grateful to Mr. Jong-Seok Kang and Mr. Taehyeon Kwon for elementary analyses. This study was supported by Open Laboratory Operational Business Developing and Diffusing the Regional Specialization Technology funded by the Busan Institute of S&T Evaluation and Planning (BISTEP). This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education [NRF-2018R1D1A1B07048150]. This work has supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) [NRF-2018R1C1B6002503]. This research was supported by Basic Science Research Capacity Enhancement Project through Korea Basic Science Institute (National research Facilities and Equipment Center) grant funded by the Ministry of Education [grant No. 2019R1A6C1010044].